Submit a Manuscript: http://www.wjgnet.
com/esps/ World J Gastroenterol 2014 August 14; 20(30): 10368-10382
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx
DOI: 10.3748/wjg.v20.i30.10368
WJG 20th Anniversary Special Issues (6): Helicobacter pylori
Medicinal plant activity on Helicobacter pylori related
diseases
Yuan-Chuen Wang
Yuan-Chuen Wang, Department of Food Science and Biotech-
nology, National Chung Hsing University, Taichung 402, Taiwan
Author contributions: Wang YC designed and performed this
research, and wrote this paper.
Correspondence to: Yuan-Chuen Wang, Professor, PhD,
Department of Food Science and Biotechnology, National Chung
Hsing University, 250 Kuo-Kuang Rd., Taichung 402,
Taiwan. ycwang@nchu.edu.tw
Telephone: +886-4-22840385 Fax: +886-4-22854053
Received: October 24, 2013  Revised: January 17, 2014
Accepted: April 1, 2014
Published online: August 14, 2014
Abstract
More than 50% of the world population is infected with
Helicobacter pylori (H. pylori ). The bacterium highly
links to peptic ulcer diseases and duodenal ulcer, which
was classified as a group Ⅰ carcinogen in 1994 by the
WHO. The pathogenesis of H. pylori is contributed by
its virulence factors including urease, flagella, vacu-
olating cytotoxin A (VacA), cytotoxin-associated gene
antigen (Cag A), and others. Of those virulence factors,
VacA and CagA play the key roles. Infection with H.
pylori vacA -positive strains can lead to vacuolation and
apoptosis, whereas infection with cagA-positive strains
might result in severe gastric inflammation and gastric
cancer. Numerous medicinal plants have been reported
for their anti-H. pylori activity, and the relevant active
compounds including polyphenols, flavonoids, qui-
nones, coumarins, terpenoids, and alkaloids have been
studied. The anti-H. pylori action mechanisms, includ-
ing inhibition of enzymatic (urease, DNA gyrase, dihy-
drofolate reductase, N -acetyltransferase, and myeloper-
oxidase) and adhesive activities, high redox potential,
and hydrophilic/hydrophobic natures of compounds,
have also been discussed in detail. H. pylori -induced
gastric inflammation may progress to superficial gastri-
tis, atrophic gastritis, and finally gastric cancer. Many
natural products have anti-H. pylori -induced inflam-
WJG|www.wjgnet.com
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
© 2014 Baishideng Publishing Group Inc. All rights reserved.
TOPIC HIGHLIGHT
mation activity and the relevant mechanisms include
suppression of nuclear factor-κB and mitogen-activated
protein kinase pathway activation and inhibition of
oxidative stress. Anti-H. pylori induced gastric inflam-
matory effects of plant products, including quercetin,
apigenin, carotenoids-rich algae, tea product, garlic
extract, apple peel polyphenol, and finger-root extract,
have been documented. In conclusion, many medicinal
plant products possess anti-H. pylori activity as well as
an anti-H. pylori -induced gastric inflammatory effect.
Those plant products have showed great potential as
pharmaceutical candidates for H. pylori eradication and
H. pylori induced related gastric disease prevention.
© 2014 Baishideng Publishing Group Inc. All rights reserved.
Key words: Helicobacter pylori ; Virulence factor; Medici-
nal plant; Active compound; Mechanism; Inflammation;
Gastric cancer; nuclear factor-κB pathway
Core tip: Many medicinal plant products possess anti-
Helicobacter pylori (H. pylori ) activity as well as an
anti-H. pylori induced gastric inflammatory effect.
Those plant products have showed great potential as
pharmaceutical candidates for H. pylori eradication and
H. pylori induced related gastric disease prevention.
Wang YC. Medicinal plant activity on Helicobacter pylori re-
lated diseases. World J Gastroenterol 2014; 20(30): 10368-10382
Available from: URL: http://www.wjgnet.com/1007-9327/full/
v20/i30/10368.htm DOI: http://dx.doi.org/10.3748/wjg.v20.
i30.10368
INTRODUCTION
Helicobacter pylori (H. pylori) is a spiral-shaped, Gram-nega-
tive, microaerophilic bacterium with 4 to 6 flagalla whose
ecological niche is the human stomach. The bacterium
10368 August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases

Table 1 Virulence factors of Helicobacter pylori

[4-7] VacA
The vacA gene (3.9 kb) encodes the VacA protein and is
Virulence factor Function present in all H. pylori strains. The protoxin of VacA is
H. pylori colonization initially a 140 kDa protein, which undergoes both N-ter-
Urease Buffers stomach acid, toxic effect on minal and C-terminal cleavages to yield an N-terminal
epithelium cells, disrupting cell tight signal sequence (33 residues), a mature 88-kDa secreted
junctions, and sheathing antigen
toxin (p88), a small secreted peptide with unknown func-
Flagella Active movements through mucin
BabA Adhesin
tion, and a C-terminal autotransporter domain. The sig-
H. pylori survival nal sequence is characterized by allelic variation with s1a,
Nox1 Resistance to killing by phagocytes, infected- s1b, and s2, which contributes to the recognization of
site inflammation the inner membrane receptor of target cells. The mature
Superoxide dismutase Resistance to killing by phagocytes
Catalase Resistance to killing by phagocytes
p88 divides into subunits N-terminal 33 kDa (p33) and
Phospholipase A Digest phospholipids in cell membranes a C-terminal 55 kDa (p55) with noncovalent bonding.
Alcohol dehydrogenase Gastric mucosal injury The N-terminal 32 hydrophobic residues of p33 play a
Tissue inflammation and damage key role in cytoplasmic membrane insertion, and p55 is
Vac A Cytotoxicity
essential for the toxin to bind to the plasma membrane.
cag PAI 31 genes coding for type Ⅳ secretion system
CagA Immunodominant antigen (part of cag PAI)
The p55 is also an allelic variation with m1 and m2. The
OipA Induce inflammation, especially for IL-8 strains with vacA s1/m1 alleles are more strongly associ-
DupA Induce inflammation via CagA, OipA and/or ated with gastric epithelial damage and gastric ulcers[5,8-13].
VacA As shown in Figure 1A, oligomer p88 forms anion-
HP-NAP Neutrophil activation
Lewis x and y antigens Molecular mimicry, autoimmunity
selective channels in the cytoplasmic membrane, which
LPS Low toxicity can further react with early and late endosomal compart-
Other ments (EE/LE) to form anion-selective channels in the
IceA Homolog of type Ⅱ restriction endonuclease vacuole membrane. Such channels increase permeability
to small organic molecules and cations Fe3+/Ni2+ which
H. pylori: Helicobacter pylori; BabA: Blood-group-antigen-binding adhesion;
can further interact with NH4+ from H. pylori generating
CagA: Cytotoxin associated gene antigen; DupA: Duodenal ulcer promot-
ing A; HP-NAP: H. pylori neutrophil activation protein; IceA: Induced by
an osmotic force for the driving water influx and vesicle
contact with epithelium factor antigen; LPS: Lipopolysaccharide; Nox1: swelling, and finally leads vacuolation[5,8-12]. On the other
NADPH oxidase 1; OipA: Outer inflammatory protein A; Vac A: Vacuolat- hand, the p88/EE/LE complex could be activated by
ing cytotoxin A; IL: Interleukin. Bax and Bak, resulting in mitochondrial transmembrane
potential (ΔΨm) disruption, followed by the release of
was first isolated from the gastric mucosa of gastritis pa- cytochrome c from mitochondria to cytoplasm, activation
tients by Marshall and Warren in 1983[1]. More than 50% of caspase-9 and caspase-3, and finally proceeding to
of the world population is infected with H. pylori. The apoptosis[10-12,14-17]. However, that apoptosis is inhibited by
bacterium highly links to peptic ulcer diseases (PUD) and CagA (Figure 1C)[11,14,18].
duodenal ulcers. Ten to fifty percent of infected individu-
als develop PUD, and 1%-3% of PUD patients progress CagA
to gastric cancer[2]. The gastric cancer risk in H. pylori- Cag A, a 120 to 145 KDa protein, is encoded on the
infected people was 2 to 7 times of that of the uninfect- cag pathogenicity island (cag PAI) which is a 40 kb locus
ed. Over half of gastric cancer patients have associated (containing 31 genes) that encodes for a type Ⅳ secretion
H. pylori infection[3,4]. The WHO classified H. pylori as a system (T4SS), and is the only known effector protein
group Ⅰ carcinogen in 1994[3]. to be injected into host cells[4,12,19,20]. Infection with cagA
positive H. pylori strains has a high rate of severe gastric
inflammation, gastritis, atrophic gastritis, and gastric
VIRULENCE FACTORS OF H. PYLORI adenocarcinoma[3,4,12,19-24]. Approximately 60%-70% of
The pathogenesis of H. pylori is caused by its virulence isolates are cagA positive. However, this rate varies geo-
factors shown in Table 1. Those virulence factors are graphically, to nearly 100% for East Asian countries and
responsible for H. pylori colonization [urease, flagella, and 60% for Western patients[4,21].
blood-group-antigen-binding adhesion (BabA)] and sur-
vival [NADPH oxidase 1 (Nox1), superoxide dismutase, nuclear factor-κB (NF-κB) pathway: Cag A is a mul-
catalase, phospholipase A, alcohol dehydrogenase] as well tiple effector via phosphorylation independent and de-
as infected tissue inflammation and even damage [Vac A, pendent pathways (Figure 1B and C). Once H. pylori ad-
Cag A, outer inflammatory protein A (OipA), duodenal heres to the host’s gastric epithelial cells, CagA is injected
ulcer promoting A (DupA), H. pylori neutrophil activation into cytosol through T4SS to activate NF-κB-inducing
protein (HP-NAP), Lewis x and y antigens, and lipopoly- kinase (NIK) and IκB kinase α/β (IKKα/β) resulting in
saccharide (LPS)][4-7]. Of those virulence factors, VacA subunit IκBα of NF-κB (trimer IκBα/p50/p60) phos-
and CagA play the key roles. phorylation and then degradation[8,12,19,25-28]. Active NF-

WJG|www.wjgnet.com 10369 August 14, 2014|Volume 20|Issue 30|

 Wang YC. Medicinal plants and H. pylori -induced diseases

A
C B
VacA (p10/p88) CagA
LPS TNF-α IL-1
p33/p55 Muropeptide
T4SS TLR4

P33/P55-EE/LE complex CagA

ases
l kin n
Bax/Bak activation c o r Ab orylatio NIK
Sr spph Muropeptide
pho Ras
ΔΨm disruption NOD-1
CagA /Sos/Grb2/Ras
Vacuolation p-CagA
PAK1 NIK IKKα/β
Cyt c release Raf
SHP-2
MKK3/6
MKK4 NF-κB (IκBα/p50/p65)
Caspase activation MEK1/2
IκBα-P
P38
JNK degradation
ERK1/2
Apoptosis

D phox Cell proliferation

gp91 phox
p-p47 Oxidative
stress
p40
phox
AP-1 (Fos/Jun)
2
O p50/p65
Nox1 Elk-1/SRE
Rac-1/GPT
-.
O2 phox
p67
Chemokine: IL-8 Cytokines (IL-6, INF-γ, TNF-α) Inflammatory factors:
H2O2 H2O2 ICAM-1, COX-2, iNOS

phox
Vascular epithelial cell
p22
ICAM-1 Activation

CD11b/CD18
Neutrophil E
Neutrophil-(CD11b/CD18)-ICAM-1

Figure 1 Signal transduction and immune response in Helicobacter pylori infected gastric epithelial cells. A: VacA-induced apoptosis; B: NF-κB pathway; C:
Mitogen-activated protein kinase pathway; D: Nox-1 pathway; E: IL-8/neutrophil pathway[5,8-12,14-17,19,25-39]. LPS: Lipopolysaccharide; IL: Interleukin; TLR4: Toll-like receptor 4;
NF-κB: Nuclear factor-kappaB; NIK: NF-κB-inducing kinase; VacA: Vacuolating cytotoxin A; CagA: Cytotoxin-associated gene antigen; PAK1: p21-activated kinase; IKKα/β:
IκB kinase α/β; MAPK: Mitogen-activated protein kinase; MKK4: MAPK kinase 4; MEK1/2: MAPK/ERK kinase 1/2; INF-γ: Interferon-γ; TNF-α: Tumor necrosis factor-α;
NOD1: Nucleotide-binding oligomerisation domain protein 1; COX-2: Cyclooxygenase-2; ICAM-1: Intercellular adhesion molecule-1; iNOS: Inducible nitric oxide synthase.

κB (dimer p50/p60) translocates into the nucleus to tran-
scribe the inflammatory factor genes [cyclooxygenase-2
(COX-2), intercellular adhesion molecule-1 (ICAM-1),
and inducible nitric oxide synthase (iNOS)], proinflam-
matory cytokine genes [interleukin-6 (IL-6), interferon-γ
(INF-γ), and tumor necrosis factor-α (TNF-α)], and che-
mokine IL-8 gene[8,19,25,27,29-31]. This is called the NF-κB
pathway (Figure 1B). All of those related proteins can
result in severe inflammation for infected cells. H. pylori
muropeptide can also enter into cytosol through T4SS
to bind with nucleotide-binding oligomerisation domain
protein 1 (NOD1), and thereafter activates NF-κB[12,28,29].
On the other hand, H. pylori LPS, TNF-α, and IL-1 can
enter into cell cytosol via toll-like receptor 4 (TLR4) to
initiate the NF-κB pathway (Figure 1B)[19,25,27,29,30].
cellular signal regulated kinase 1/2 (ERK1/2), and p38
kinase, for which the JNK pathway involves p21-acti-
vated kinase (PAK1), mitogen-activated protein (MAP)
kinase kinase 4 (MKK4), and JNK; the p38 pathway
involves MAP kinase 3/6 (MKK3/6) and p38; and the
MEK/ERK pathway involves complex CagA/son of
sevenless/growth factor receptor bound 2/rat sarcoma
(CagA/Sos/Grb2/Ras), Raf, MAPK/ERK kinase 1/2
(MEK1/2), and ERK1/2. The MAPK cascades lead to
transcription factor [activator protein 1 (AP-1), Elk-1/
serum response element (Elk-1/SRE), Nox1, and NF-
κB] activation, leading to translation of chemokine IL-8,
cytokines (IL-6, TNF-α, INF-γ), and inflammatory fac-
tors (COX-2, ICAM-1, and iNOS) as well as NADPH
oxidase activation[27-29,31-35].

mitogen-activated protein kinase pathway (MAPK): Nox-1 pathway: The Nox-1 family consists of members
Aside from the NF-κB pathway, MAPK pathway activa- gp91phox, p22phox, p47phox, p67phox, and p40phox, in which
tion is induced by CagA (Figure 1C). MAPK concerns gp91phox and p22phox persist in cytosol, and p40phox, p47phox,
three key kinases: C-terminal Jun-kinase (JNK), extra- and p67phox are located in the cell membrane[36,37]. When

WJG|www.wjgnet.com 10370 August 14, 2014|Volume 20|Issue 30|


a host cell is attacked by H. pylori, p47phox is immediately
phosphorylated (p-p47) along with p67phox, p40phox, and
GTPase-Rac to translocate to the cell membrane to form
a gp91phox/p22phox/p-p47phox/p67phox/p40phox/GTPase-
Rac complex, an active NADPH oxidase. Active p67phox
oxidizes NADPH to NADP+ and H+ which pass through
gp91phox and are released to the environment; at the same
time, gp91phox reduces O2 to O2-. and follows hydrogen
peroxide production, resulting in oxidative stress in the H.
pylori infected cells (Figure 1D)[33,35,38,39].
SHP-2/ERK pathway~CagA phosphorylation de-
pendent: With exception to the CagA independent path-
way, CagA can suffer phosphorylation by Src and Ab1
kinases, and then forms a complex with Src homology 2
(SH2)-domain containing protein tyrosine phosphatase
(SHP-2) to activate ERK1/2 (Figure 1C). Both MEK/
ERK and SHP-2/ERK pathways not only lead to NF-
κB (Figure 1B) and Nox1 (Figure 1D) activation, but also
result in cell proliferation (Figure 1C)[12,19-21,28,29].
IL-8
As aforementioned, IL-8 is a chemokine which is regu-
lated by the transcription factors NF-κB, AP-1, and Elk/
SRE. IL-8 plays a key role in H. pylori infection and is an
important feature in H. pylori-infected patients. As shown
in Figure 1E, IL-8 infiltrates into vascular endothelial cells
to activate the CD11b/CD18 dimer. The active CD11b/
CD18 dimer forms a complex with neutrophil (CD11b/
CD18/neutrophil), and then further binds to ICAM-1 on
the vascular endothelial cell membrane (CD11b/CD18/
neutrophil/ICAM-1). That tetramer (CD11b/CD18/
neutrophil/ICAM-1) infiltrates into gastric epithelial cells
and releases high amounts of ROS (O2-., H2O2, HOCl,
OH•, and 1O2) through neutrophil NADPH oxidase,
resulting in oxidative burst[27,29,33,40]. Additionally, IL-8 can
activate polymorphonuclear cells and/or macrophages
to produce IL-12 which further amplifies the T-cell re-
sponse to H. pylori[29].
ANTI-H. PYLORI ACTIVITY OF
MEDICINAL PLANTS
Various pharmacological regimens have been studied
in the treatment of H. pylori infection. Antibiotics[41,42],
proton-pump inhibitors[43,44], H2-blockers[45,46], and bis-
muth salts[47] are suggested standard treatment modalities,
which are typically combined in dual, triple, and quadru-
ple therapy regimens in order to eradicate H. pylori infec-
tion[41,48]. Some problems may arise upon administration
of those eradication regimens, i.e. the cost[48], the efficacy
of antibiotics regarding the pH (for instance, amoxicillin
is most active at a neutral pH and tetracycline has greater
activity at a low pH)[48] and resistance to the antibiot-
ics[49-51]. Therefore, some patients undergoing such drug
regimens experienced therapeutic failure.
WJG|www.wjgnet.com
Wang YC. Medicinal plants and H. pylori -induced diseases
Plant extracts and fractions
Numerous studies have been carried out to investigate
the anti-H. pylori activity of plant extracts, partially puri-
fied fractions, natural compounds, and synthetic com-
pounds. Anti-H. pylori activity for the medicinal plant
extracts and partially purified fractions is listed in Table
2, which has those results categorized as 4 classes accord-
ing to their minimum inhibitory concentration (MIC): (1)
strong activity (MIC: < 10 μg/mL); (2) strong-moderate
activity (MIC: 10-100 μg/mL); (3) weak-moderate activ-
ity (MIC: 100-1000 μg/mL); and (4) weak activity (MIC:
>1000 μg/mL). In Table 2, 34 studies including more
than 80 plants were collected. Surprisingly, only a few
studies exhibited strong (2.9%, 1/34)[52] and strong-mod-
erate (11.8%, 4/34)[53-57] activity. Most studies revealed
weak-moderate (50%, 17/34) [58-73] and weak (32.4%,
11/34)[74-81] activity against H. pylori. Notably, a few plant
extracts possessed strong anti-H. pylori activity. The great-
est of them was Impatiens balsamina L. (Balsaminaceae),
a Taiwanese folk medicinal plant. The acetone, 95%
ethanol, and ethyl acetate pod extracts showed strong
anti-H. pylori activity with 1.25-2.5 μg/mL of MICs and
1.25-5.0 μg/mL of minimum bactericidal concentrations
(MBCs) against multiple-antibiotic [clarithromycin (CLR),
metronidazole (MTZ), and levofloxacin (LVX)] resistant
H. pylori strains. Such activity exceeded that of MTZ and
approximated that of amoxicillin (AMX), one of the
most effective drugs used in the eradication of H. pylori
infection worldwide[52]. The Persea Americana Mill. (Laura-
ceae), a Mexican medicinal plant, in methanol extract also
showed strong anti-H. pylori activity with < 7.5 μg/mL
of MIC[53]. Remarkable anti-H. pylori activity was reported
for three Paskin indigenous medicinal plant extracts: the
Acacia nilotica (L.) Delile (Fabaceae) aqueous extract, the
Fagonia arabica L. (Zygophyllaceae) acetone extract, and
the Casuarina equisetifolia L. (Casuarinaceae) methanol ex-
tract, all of them having 8 μg/mL of MIC[61]. The chlo-
roform fractions from the methanol extracts of Centaurea
solstitialis ssp. Solstitialis and Centaurea solstitialis ssp. solstitia-
lis (flowers) also exhibited significantly lower MIC (1.95
μg/mL) against H. pylori, both plants having been used as
Turkish anti-ulcerogenic folk remedies[59]. The leaf hex-
ane fraction of Aristolochia paucinervis Pomel, a Moroccan
medicinal plant, demonstrated higher inhibitory activity
(MIC: 4 μg/mL) against H. pylori[58].
Natural compounds from plants
Aside from plant extracts, much literature has reported
on the anti-H. pylori activity of plant compounds. Table 3
lists 28 studies including 131 compounds to address their
anti-H. pylori activity in which phenolics/simple phenols/
polyphenols, flavonoids, quinones, coumarins, terpenoids,
alkaloids, and other compounds are involved. Some of
these compounds’ chemical structures are shown in Fig-
ure 2. Notably, MICs for those compounds were much
lower than those of plant extracts (Table 2), over 50% of
which being lower than 10 μg/mL. Specifically, of those
10371 August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases

Table 2 Anti-Helicobacter pylori activity of medicinal plant extracts and fractions

Plant Test sample MIC/MBC Ref.

Strong activity (MIC: < 10 μg/mL)
Impatiens balsamina L. Pod acetone/95% ethanol/ MIC: 0.625-2.5 μg/mL Wang et al[52]
ethyl acetate extracts MBC: 1.25-2.5 μg/mL
Strong-moderate acticity (MIC: 10-100 μg/mL)
Persea americana, Annona cherimola, Guaiacum coulteri, Methanol extract MIC: 7.5-15.6 μg/mL Castillo-Juárez et al[53]
Moussonia deppeana
Myristica fragrans (seed), Rosmarinus officinalis (rosemary leaf ) Methanol extract MIC: 12.5-25 μg/mL Mahady et al[54]
Curcuma amada Roxb., Mallotus phillipinesis (Lam) Muell., 70% Ethanol extract MIC: 15.6-62.5 μg/mL Zaidi et al[55]
Myrisctica fragrans Houtt., Psoralea corylifolia L.
Achillea millefolium, Foeniculum vulgare (seed), Methanol extract MIC: 50 μg/mL Mahady et al[54]
Passiflora incarnata (herb), Origanum majorana (herb) and
a (1:1) combination of Curcuma longa (root), ginger rhizome
Carum carvi (seed), Elettaria cardamomum (seed), Methanol extract MIC: 100 μg/mL Mahady et al[54]
Gentiana lutea (roots), Juniper communis (berry),
Lavandula angustifolia (flowers), Melissa officinalis (leaves),
Mentha piperita (leaves), Pimpinella anisum (seed)
Abrus cantoniensis, Saussurea lappa, Eugenia caryophyllata Ethanol extract MIC: 40 μg/mL Li et al[56]
Hippophae rhamnoides, Fritillaria thunbergii, Magnolia officinalis, Ethanol extract MIC: 60 μg/mL Li et al[56]
Schisandra chinensis, Corydalis yanhusuo, Citrus reticulata,
Bupleurum chinense, Ligusticum chuanxiong
Myroxylon peruiferum Methanol extract MIC: 62.5 μg/mL Ohsaki et al[57]
Weak-moderate acticity (MIC: 100-1000 μg/mL)
Aristolochia pauciner6is Rhizome/leave fraction MIC: 4-128 μg/mL Gadhi et al[58]
Cistus laurifolius, Spartium junceum, Cedrus libani, solstitialis, Solvent extract and hexane MIC: 1.95-250 μg/mL Yeşilada et al[59]
Momordica charantia, Sambucus ebulus, Hypericum perforatum fraction
Larrea divaricate Cav (leaves and tender branches) Aqueous extract MIC: 40-100 μg/mL Stege et al[60]
Acacia nilotica (L.) Delile, Calotropis procera (Aiton) Methanol/acetone extract MIC: 8-256 μg/mL Amin et al[61]
W.T. Aiton, Fagonia arabica L., Adhatoda vasica Nees,
Casuarina equisetifolia L.
Zingiber officinale 95% Ethanol extract MIC: 10-160 μg/mL Nostro et al[62]
Tephrosia purpurea (Linn.) Pers. Methanol extract and fraction MIC: 25-400 μg/mL Chinniah et al[63]
Terminalia macroptera (root) Root solvent fraction MIC: 100-200 μg/mL Silva et al[64]
Black myrobalan (Teminalia chebula Retz) Water extract MIC: 125 μg/mL Malekzadeh et al[65]
MBC: 150 μg/mL
Rubus ulmifolius leaves Ethyl acetate/methanol MIC: 134-270 μg/mL Martinia et al[66]
Amphipterygium adstringens Bark petroleum ether fraction MIC: 160 μg/mL Castillo-Juárez et al[67]
Lycopodium cernuum Hexane fraction MIC: 16-1000 μg/mL Ndip et al[68]
MBC: 125-1000 μg/mL
Ageratum conyzoides, Scleria striatinux, Lycopodium cernua Methanol extract MIC: 63-1000 μg/mL Ndip et al[69]
MBC: 195-15000 μg/mL
Sclerocarya birrea Acetone/aqueous stem bark MIC: 80-2500 μg/mL Njume et al[70]
extract
Including Artemisia ludoviciana subsp.mexicana 43 plants Methanol/aqueous extract MIC: 312-500 μg/mL Castillo-Juárez et al[53]
Pteleopsis suberosa Stem bark methanol extract MIC: 313-500 μg/mL Germanò et al[71]
Ageratum conyzoides, Scleria striatinux, Lycopodium cernua Methanol extract MIC: 32-1000 μg/mL Ndip et al[69]
Including Cuminum cyminum L., Cynara scolymus L., Ethanol extracts MIC: 600-10000 μg/mL Nostro et al[72]
Origanum vulgare L. 17 plants
Allium sativum Aqueous extract MIC: 2000-5000 μg/mL Cellini et al[73]
Weak acticity (MIC: > 1000 μg/mL)
Mentha × piperita, Peppermint Oil, Origanum vulgare, Essential oil IC50: 160-1460 μg/mL Cwikla et al[74]
Pimpinella anisum, Aniseed Oil, Syzygium aromaticum
Chamomila recutita L., Ilex paraguariensis A. St.-Hil. 96% Ethanol extract MIC: < 625-1250 μg/mL Cogo et al[75]
Allium ascalonicum Linn. (leaf) Methanol extract MIC: 625- 1250 μg/mL Bolanle et al[76]
Sclerocarya birrea Stem bark acetone/aqueous MIC90: 60-2500 μg/mL Njume et al[70]
extracts
Punica granatum, Quercus infectoria Ethanol extract MIC: 160-> 2500 μg/mL Voravuthikunchai et al[77]
Mentha × piperita, Peppermint Oil, Origanum vulgare, Essential oil IC50: 160-1460 μg/mL Cwikla et al[74]
Pimpinella anisum, Aniseed Oil, Syzygium aromaticum
Including Anthemis melanolepis 13 plants 70% Methanol extract MIC: 625-5000 μg/mL Stamatis et al[78]
Including Cuminum cyminum L. 17 plants Ethanol extract MIC: 75-10000 μg/mL Nostro et al[72]
Plumbago zeylanica L. Acetone extract MIC: 320-10240 μg/mL Wang and Huang[79]
MBC: 5120-81920 μg/mL
Anisomeles indica (L.) O. Kuntze, Alpinia speciosa (Wendl.) K. Schum., 95% Ethanol extract MIC: 640-10240 μg/mL Wang and Huang[80]
Bombax malabaricum DC., Paederia scandens (Lour.) Merr.
Allium sativum Aqueous extract MIC: 0.1% (v/v) Cellini et al[73]
Including Cymbopogon citratus (lemongrass) 13 plants Essential oil Ohno et al[81]

MIC: Minimum inhibitory concentration; MBC: Minimum bactericidal concentration.

WJG|www.wjgnet.com 10372 August 14, 2014|Volume 20|Issue 30|


compounds, 5 compounds [2-methoxy-1,4-naphtho-
quinone (MeONQ)[95], terpinen-4-ol[106], pyrrolidine[106],
1-methyl-2-[(Z)-8-tridecenyl]-4-(1H)-quinolone[107], and
1-methyl-2-[(Z)-7-tridecenyl]-4-(1H)-quinolone[107]] of
MICs or 50% MICs (MIC50) were lower than 1 μg/mL,
which were similar to or lower than that of AMX.
Phenolics, simple phenols, and polyphenols: Pheno-
lic compounds are commonly distributed in plants. They
are classified as phenolics, simple phenols, and polyphe-
nols. Cinnamic acid and chlorogenic acid are the com-
mon representatives of phenolics (Figure 2). Tannin is a
group of polymeric phenolic substances, which is divided
into two categories based on their chemical nature: hy-
drolyzable and condensed tannins (Figure 2). As listed on
Table 3, boropinic acid (a cinnamic acid derivative from
Boronia pinnata Sm.) had the lowest MIC (1.62 μg/mL)[82];
MICs for corilagin (a hydrolyzable tannin from Geranium
wilfordii) against 6 H. pylori strains were 2-4 μg/mL[83]; el-
lagic acid (a hydroxydiphenic acid from Rubus ulmifolius
leaves) showed anti-H. pylori activity with 2-10 μg/mL
of MICs[66], whereas 3-farnesyl-2-hydroxybenzoic acid
(a hydroxybenzoic acid prenylated derivative from Piper
multiplinervium) had 3.75-12.5 μg/mL of MICs against 5 H.
pylori strains[84].
Flavonoids: Flavonoids are widely distributed through-
out the plant kingdom. The family consists of 7 mem-
bers: flavones, flavanones, flavonols, flavanols, flavan-
3-ols (the structural unit of condensed tannins),
anthocyanidins, and chalcones with C6-C3-C6 skeleton
feature (Figure 2). As indicated in Table 3, the lowest
MICs of flavonoids against H. pylori peaked at querce-
tin 3-methyl ether (isorhamnetin) (MIC: 3.9 μg/mL),
a methoxylated flavonol aglycone from Cistus laurifolius
leaves[93]; kaempferol, a flavonol from Rubus ulmifolius
leaves (MBC: 6 μg/mL)[66]; and cabreuvin, an isoflavone
derivative from Myroxylon peruiferum (MIC: 7.8 μg/mL)[57].
Quinones: Quinones are aromatic rings with two ketone
substitutions (Figure 2). These compounds, largely re-
sponsible for flower color, are ubiquitous in nature and
highly reactive. In Table 3, MeONQ (a naphthoquinone
isolated from I. balsamina L.) has the strongest anti-H.
pylori action of those quinones with 0.156-0.625 μg/mL
of MICs and 0.313-0.625 μ g/mL of MBCs against
multiple-antibiotic (CLR, MTZ, and LVX) resistant H.
pylori strains. The activity was equivalent to that of AMX
as well as not being influenced by pH (4-8) or heat (121 ℃
for 15 min) treatments. Interestingly, MeONQ abounds
in the I. balsamina L. pod at the level of 4.39% (w/w)[95].
Subsequently, 2-(hydroxymethyl)anthraquinone followed,
which is an anthraquinone isolated from Tabebuia impetigi-
nosa Martius ex DC (Taheebo) with 2 μg/mL of MIC[96].
Coumarins: The chemical structure of coumarins are
benzene fused with an α-pyrone ring (Figure 2), which
are responsible for the characteristic odor of hay[112].
WJG|www.wjgnet.com
Wang YC. Medicinal plants and H. pylori -induced diseases
Coumarins are widely found in plants. Basile et al[99] re-
ported that aegelinol and its derivative [benzoyl aegelinol
isolated from Ferulago campestris (Apiaceae) roots] showed
anti-H. pylori activity with 5-25 μg/mL of MIC. In fact,
many coumarin derivatives are synthetic and are com-
mercially sold as supplementary diet products. Jadhav et
al[100] and Kawase et al[101] studied the anti-H. pylori activity
of 23 and 24 synthetic coumarin derivatives, respectively,
wherein they found those coumarin derivatives to have
anti-inhibitory activity, but not particularly high (MIC: 10
to > 100 μg/mL).
Terpenoids: Terpenoids derived from terpenes contain-
ing oxygen in molecule. Isoprene is the basic structural
unit of terpenes. Monoterpenes (C 10H 16), diterpenes
(C20), triterpenes (C30), and tetraterpenes (C40) com-
monly occur in nature (Figure 2). Arjunglucoside I is an
oleanane saponine isolated from Pteleopsis suberosa Engl.
Et Diels stem bark (Combretaceae), which possesses
anti-H. pylori activity (MIC: 1.9-7.8 μg/mL) against vacA/
cagA positive and metronidazole-resistant strains [102].
Trichorabdal A (a diterpene from Rabdosia trichocarpa)
showed strong anti-H. pylori activity with 2-5 μg/mL of
MICs[103]. A remarkable anti-H. pylori compound, terpin-
en-4-ol, was isolated from Sclerocarya birrea (Anacardiaceae)
with 0.004-0.06 μg/mL of MIC50, being similar to that of
AMX (MIC50: 0.0003-0.06 μg/mL)[106].
Alkaloids: Heterocyclic nitrogen compounds are called
alkaloids (Figure 2). The first pharmaceutically used
alkaloid was porphine from the opium poppy Papaver
somniferum [112]. 1-Methyl-2-[(Z)-8-tridecenyl]-4-(1H)-
quinolone and 1-methyl-2-[(Z)-7-tridecenyl]-4-(1H)-
quinolone were isolated from Evodia rutaecarpa fruits tra-
ditionally used in Chinese medicine. Both alkaloids were
found to have the relatively low MIC against H. pylori (<
0.05 μg/mL), which was similar to AMX and CLR[107].
Mechanisms of anti-H. pylori action
As aforementioned, numerous studies have reported nat-
ural products’ anti-H. pylori activity. However, only a few
papers have concerned the action mechanisms. Within
this literature, the mechanisms include urease activity
inhibition, anti-adhesion activity, DNA damage, protein
synthesis inhibition, and oxidative stress, which are each
addressed below.
Urease activity inhibition: Both Acacia nilotica and
Calotropis procera extracts possessed anti-H. pylori activ-
ity possibly due to inhibition of urease activity through
competitive and mixed type mechanisms, respectively, in
which both Vmax and affinity (Km) were changed for the
latter type[61]. The anti-H. pylori actions of 1,2,3,4,6-penta-
O-galloyl-β -D-glucopyranose from Paeonia lactiflora roots
were considered to work in multiple manners. The hydro-
phobicity of the compound facilitates it to bind to cell
membranes resulting in the loss of membrane integrity as
well as inhibition of urease activity and UreB (an adhesin)
10373 August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases

Table 3 Anti-Helicobacter pylori activity of compounds from plants

Compound Original plant MIC/MBC Ref.

Phenolics/Simple phenols/Polyphenols
Boropinic acid Boronia pinnata MIC: 1.62 μg/mL Epifano et al[82]
Sm.
Corilagin, 1,2,3,6-tetra-O-galloyl-b-D-glucose Geranium wilfordii MIC: 2-8 μg/mL Zhang et al[83]
Egallic acid Rubus ulmifolius leaves MIC: 2-10 μg/mL Martinia et al[66]
3-Farnesyl-2-hydroxybenzoic acid Piper multiplinervium MIC: 3.75-12.5 μg/mL Rüegg et al[84]
Epigallocatechin gallate, epicatechin gallate, epigallocatechin, MIC: 8-256 μg/mL Mabe et al[85]
epicatechin
Magnolol Magnoliae officinalis MIC: 10-20 μg/mL Bae et al[86]
Psoracorylifols Psoralea corylifolia MIC: 12.5-25 μg/mL Yin et al[87]
Resveratrol Red wine MIC: 25-100 μg/mL Paulo et al[88]
Cinnamic acid MIC: 80-200 μg/mL Bae et al[86]
Allixin Allium sativum MIC90: 50 μg/mL Mahady et al[89]
Paeonol, benzoic acid, methyl gallate, Paeonia lactiflora Roots MIC: 80-320 μg/mL Ngan et al[90]
1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose MBC: 320-1280 μg/mL
Including 3-hydroxy-2,2-dimethyl-8-prenylchromane-6-propenoic Brazilian propolis MIC: 130-1000 μg/mL Banskota et al[91]
acid 10 phenolic acids
Chlorogenic acid Anthemis altissima MIC: 312.5-1250 μg/mL Konstantinopoulou et al[92]
Flavonoids
Quercetin 3-methyl ether, Cistus laurifolius leaves MIC: 3.9-62.5 μg/mL Ustün et al[93]
quercetin 3,7-dimethyl ether, kaempferol 3,7-dimethyl ether
Kaempferol Rubus ulmifolius leaves MBC: 6 μg/mL Martinia et al[66]
Kaempferol 4’-methyl ether, quercetin, rhamnetin, isoquercetrin, Anthemis altissima MIC: 6.25-50 μg/mL Konstantinopoulou et al[92]
taxifolin, eriodictyol
Including licoisoflavone B and licoricidin 16 flavonoids Licorice MIC: 6.25-50 μg/mL Fukai et al[94]
Cabreuvin Myroxylon peruiferum MIC: 7.8 μg/mL Ohsaki et al[57]
3,5,7-Trihydroxy-4’-methoxyflavanol, keampferol-3,4’-dimethyl ether Brazilian propolis MIC: 500-1000 μg/mL Banskota et al[91]
Quinones
2-Methoxy-1,4-naphthoquinone Impatiens balsamina L. MIC: 0.156-0.625 μg/mL Wang et al[95]
MBC: 0.313-0.625 μg/mL
2-(Hydroxymethyl)anthraquinone, anthraquinone-2-carboxylic acid, Tabebuia impetiginosa MIC: 2-8 μg/mL Park et al[96]
Lapachol, plumbagin Martius ex DC
Idebenone, duroquinone, menadione, juglone, benzoquinone, MIC90: 0.8-25 μg/mL Inatsu et al[97]
coenzyme Q1, coenzyme Q10, decylubiquinone
Emodin Rhei Rhizoma MIC86-99: 250 μg/mL Wang and Chung[98]
Coumarins
Benzoyl aegelinol, aegelinol Ferulago campestris MIC: 5-25 μg/mL Basile et al[99]
(Apiaceae) roots
24 Synthetic coumarin derivatives MIC: 10-40 μg/mL Jadhav et al[100]
23 Synthetic coumarin derivatives MIC50: 23->100 μg/mL Kawase et al[101]
Terpenoids
Arjunglucoside I Pteleopsis suberosa MIC: 1.9-7.8 μg/mL De Leo et al[102]
Trichorabdal Rabdosia trichocarpa MIC: 2.5-5 μg/mL Kadota et al[103]
Sivasinolide, altissin, 1-epi-tatridin B, desacetyl-β-cyclopyrethrosin, Anthemis altissima MIC: 12.5-50 μg/mL Konstantinopoulou et al[92]
tatridin-A
(Z)-R-santalol (7), (Z)-β-santalol, (Z)-lanceol Santalum album MIC: 7.8-31.3 μg/mL Ochi et al[104]
Stigmasta-7,22-diene-3β-ol Impatiens balsamina L. MIC: 20-80 μg/mL Wang et al[95]
MBC: 20-80 μg/mL
Plaunotol Plau-noi MIC90: 12.5 mg/mL Koga et al[105]
Terpinen-4-ol Sclerocarya birrea MIC50: 0.004-0.06 μg/mL Njume et al[106]
(Anacardiaceae)
Alkaloids
1-Methyl-2-[(Z)-8-tridecenyl]-4-(1H)-quinolone, Evodia rutaecarpa fruits MIC: < 0.05 μg/mL Hamasaki et al[107]
1-Methyl-2-[(Z)-7-tridecenyl]-4-(1H)-quinolone
Tryptanthrin Polygonum tinctorium MIC: 2.5 μg/mL Hashimoto et al[108]
Lour.
Other compounds
Pyrrolidine Sclerocarya birrea MIC50: 0.05-6.3 μg/mL Njume et al[106]
(Anacardiaceae)
Diallyl disulfide, diallyl trisulfide, diallyl tetrasulfide, allicin MIC: 3-100 μg/mL O’gara et al[109]
MBC: 6-200 μg/mL
Palmitoyl ascorbate MIC: 40-400 μg/mL Tabak et al[110]
Capric acid, lauric acid, myristic acid, myristoleic acid, MBC: 0.5-5 mmol/L Sun et al[111]
palmitoleic acid, linolenic acid, monolaurin, monomyristin

MIC: Minimum inhibitory concentration; MBC: Minimum bactericidal concentration.

WJG|www.wjgnet.com 10374 August 14, 2014|Volume 20|Issue 30|

 Wang YC. Medicinal plants and H. pylori -induced diseases

Phenolics and simple phenols Cinnamic acid Chlorogenic acid

HO CO2H

O O

OH HO O
OH
OH
OH
Tannins 1,2,3,6-tetra-O-β-D-galloyl-glucose (hydrolyzable tannin) Epigallocatechin gallate (condensed tannin)
OH
O
OH OH
HO
O
OH
O
O OH
HO HO O
HO O OH OH
HO O
O OH
O
OH O
O C OH
OH
OH O OH
HO OH
OH

Flavonoids Kaempferol Licoisoflavone B

OH
HO O
OH
HO O

OH OH O
O
OH O

Quinones 2-methoxy-1,4-naphthoquinone Emodin

O OH O OH

H3C OH

O O

Terpenoids Stigmasta-7,22-diene-3β-ol Erpinen-4-ol

21
22 28
1820 29
12 17 OH
11 23 24 26
19 13 16 25
1 9 14
2 27
10 8 15
3 5 7
HO 4 6

Coummarins Aegelinol 7-methoxy-4-methylcoumarin

HO

O O O
O O O

Alkaloids Methyl-2-[(Z)-8-tridecenyl]-4(1H)-quinolone (evocarpine)

Figure 2 Chemical structures of some anti-Helicobacter pylori compounds from medicinal plants.

expression[90]. The inhibitory effect of resveratrol against soluble extract (a commercial product) may be through
H. pylori was possibly due to inhibition of urease activity[88]. urease activity inhibition and disruption of energy produc-
The action mode of mixed oregano and cranberry water- tion by inhibition of proline dehydrogenase at the plasma

WJG|www.wjgnet.com 10375 August 14, 2014|Volume 20|Issue 30|

 Wang YC. Medicinal plants and H. pylori -induced diseases
membrane[113]. In an in vivo study, both the dichlorometh-
ane fraction and the ethanolic extract of Calophyllum brasil-
iense stem bark decreased the number of urease-positive
Wistar rats, which was confirmed by the reduction of H.
pylori presence in histopathological analysis[114].
Anti-adhesion activity: The turmeric, borage, and fresh
parsley water extracts were found to inhibit adhesion of
H. pylori 11637 to the human stomach section; moreover,
33.9%-61.9% of inhibition rates for antigens Lewis a
and Lewis b were observed[115]. The Glycyrrhiza glabra root
aqueous extract and polysaccharides exhibited strong
anti-adhesive activity under a fluroscent microscopy of
human gastric mucosa aliquots with fluorescent-labeled
H. pylori[116]. EPs 7630, a commercial product of the Pel-
argonium sidoides DC (Geraniaceae) root extract, showed
good anti-adhesive activity in a dose-dependent manner
(0.001-10 mg/mL)[117]. Plaunotol, an acyclic diterpene
alcohol isolated from the leaves of the plau-noi tree in
Thailand, was found to suppress adhesion of H. pylori to
adenocarcinoma cells as well as inhibit IL-8 secretion in a
dose-dependent manner[118].
Oxidative stress: MeONQ exhibited very strong bac-
tericidal H. pylori activity[95]. The possible mechanisms of
MeONQ are due to the high redox potential of the com-
pound. When MeONQ enters the cell membrane, it is
immediately metabolized by flavoenzymes and undergoes
serial redox cyclic reactions to produce a high amount
of ROS (O-•, MeONQ-•, and H2O2). Those ROS further
damage cellular macromolecules and may lead to H. pylori
death[95].
Amphiphilic nature of compounds: Anti-H. pylori
compound terpinen-4-ol from Sclerocarya birrea (Anacar-
diaceae) is a monocyclic monoterpene derivative with
amphiphilic nature. The strong anti-H. pylori activity of
the compound was thought to be a result of its hydro-
philicity and hydrophobicity. The hydrophilicity allows
this compound to diffuse through surrounding water to
the bacterial cell wall, whereas the hydrophobicity lets
this compound close in on and partially bind to the cy-
toplasmic membrane resulting in the loss of membrane
integrity[107].
Others: Glabridin (a major flavonoid of GutGards®)
exhibited anti-H. pylori activity. Additionally, GutGard®
showed a potent inhibitory effect on DNA gyrase and
dihydrofolate reductase with 4.40 and 3.33 mg/mL of
IC50, respectively[119]. Emodin (1,3,8-trihydroxy-6-meth-
ylanthraquinone), a major bioactive compound of Radix
et Rhizoma Rhei (a Chinese herb medicine), induced H.
pylori DNA damage[98]. Flavonoids vitexin, isovitexin,
rhamnopyranosylvitexin, and isoembigenin from Piper
carpunya Ruiz & Pav. showed anti-H. pylori activity. Those
compounds effectively released myeloperoxidase from
rat peritoneal leukocytes as well as inhibited of H+,K+-
ATPase activity[120]. N-Acetylation, a major metabolic
WJG|www.wjgnet.com 10376
pathway for arylamine carcinogens, is catalysed by cyto-
solic arylamine N-acetyltransferase. Rhein, one of the
bioactive component of Dahuang, effectively inhibited
N-acetyltransferase activity and H. pylori growth[121].
ANTI-H. PYLORI-INDUCED GASTRIC
INFLAMMATION OF PLANT PRODUCTS
Once H. pylori attaches to host cells, the signal trans-
duction is immediately initiated, and then transcrip-
tion/translation of the relevant inflammatory proteins,
especially for IL-8, IL-6, INF-γ, TNF-α, COX-2, and
ICAM-1, through NF-κB, MAPK, MEK/ERK, SHP-2/
ERK, and Nox-1 pathways (Figure 1). Those proteins
can further induce immune response cascades resulting in
severe H. pylori-infected gastric mucosa inflammation. As
proposed in the Correa pathway[22], the H. pylori-induced
gastric chronic inflammation can progress to superficial
gastritis, atrophic gastritis, intestinal metaplasia, dysplasia,
and finally adenocarcinoma. Specifically, atrophic gastritis
is a critical initiating step in the progression toward gas-
tric cancer[22-24]. There have been many studies focusing
on anti-H. pylori-induced inflammation and the relevant
mechanisms, in which NF-κB and MAPK pathways were
the most discussed.
Inhibition of NF-κ B pathway
The H. pylori-induced NF-κB pathway is presented in
Figure 1B. Many natural products were found to have
anti-H. pylori induced inflammation activity through the
suppression of NF-κB activation. Apigenin, one of the
most common flavonoids, is widely distributed in fruits
and vegetables, especially abound in parsley and celery.
Apigenin treatments (9.3-74 μmol/L) significantly in-
hibited NF-κB activation, thus, the IκBα expression
increased and inflammatory factor (COX-2, ICAM-1,
ROS, IL-6, and IL-8) expressions decreased. Specifically,
the ROS levels decreased partially based on the intrinsic
scavenging property of apigenin[122]. Curcumin, a natural
polyphenol, presents in turmeric. Activation-induced
cytidine deaminase (AID) is a downstream member of
NF-κB regulated by NF-κB. Curcumin significantly sup-
pressed NF-κB activation as well as IKK activation and
IκBα degradation; and therefore inhibited AID activity in
the H. pylori-infected adenocarcinoma cells[123]. Capsaicin,
a terpenoid, is an active compound of chilies and chili
peppers. The compound significantly inhibited H. pylori-
induced IL-8 production through inhibition of IKK and
NF-κB activation in a dose- and time-dependent man-
ner[124]. Caffeic acid phenethyl ester (CAPE), an active
compound of propolis, has been reported to have anti-
inflammatory and immunomodulatory properties. CAPE
inhibited H. pylori-induced NF-κB and AP-1 DNA bind-
ing activity in a dose- and time-dependent manner in H.
pylori-infected AGS cells. The suppression of NF-κB
(Figure 1B) and MAPK (Figure 1C) pathway activation
was involved, and thus TNF-α, IL-8, and COX-2 expres-
August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases
sions decreased. Additionally, CAPE also suppressed H.
pylori-induced cell proliferation[125]. San-Huang-Xie-Xin-
Tang (SHXT), a traditional oriental medicinal formula
containing Rhizoma Coptidis (Coptis chinesis Franch), Scutel-
lariae radix (Scutellaria baicalensis Georgi), and Rhei rhizome
(Rheum officinale Baill), has been used to treat gastritis,
gastric bleeding, and peptic ulcers. SHXT and baicalin (an
active compound of SHXT) was found to decrease IκBα
phosphorylation and inflammatory factor (IL-8, COX-2,
and iNOS) expressions in H. pylori-infected AGS cells,
of which the transduction factor NF-κB activation was
inhibited. SHXT and baicalin might exert anti-inflam-
matory and gastroprotective effects in H. pylori-induced
gastric inflammation[126]. Zaidi et al[127] examined the anti-
inflammatory effects of selected Pakistani medicinal
plants and found that 12 plants (including Alpinia galangal)
exhibited strong inhibitory activity against IL-8 secretion
in H. pylori-infected AGS cells at 100 μg/mL of 70% eth-
anol extracts. Moreover, significant ROS suppression was
demonstrated in the 6 included Achillea millefolium extracts.
Notably, an in vivo study of anti-inflammatory effects of
CAPE was reported by Toyoda et al[128]. CAPE has inhibi-
tory effects on H. pylori-induced gastritis in Mongolian
gerbils through the suppression of NF-κB activation in
which TNF-α, INF-γ, IL-2, IL-8, KC (IL-8 homologue),
and iNOS expressions significantly decreased.
With exception to H. pylori-induced cell inflammation,
paeoniflorin (a benzoic acid derivative from Paeonia lacti-
flora pall roots) exhibited dramatic inhibition of NF-κB
activation in a time- and dose-dependent manner in hu-
man gastric carcinoma cells (SGC-7901). Moreover, the
compound enhanced 5-fluorouracil-induced apoptosis of
the gastric carcinoma cells[129].
Inhibition of MAPK pathway
β-Carotene is a well-known carotenoid and 10-20 μmol/
L treatment doses significantly decreased p-38, JNK,
ERK1/2 phosphorylation as well as decreased DNA
binding activity of NF-κB and AP-1 in H. pylori-infected
AGS cells in a dose-dependent manner. The ROS level,
iNOS and COX-2 expressions also decreased. Both NF-
κB (Figure 1B) and MAPK (Figure 1C) pathway activa-
tion were inhibited by β-carotene[130]. As aforementioned,
curcumin significantly inhibited NF-κB activation[123].
Foryst-Ludwig et al[131] reported that curcumin inhibited
IκBα degradation, IKKα/β activity, and NF-κB DNA-
binding activity in H. pylori-infected AGS cells. Addition-
ally, JNK1/2, ERK1/2, and p38 phosphorylation were
also remarkably suppressed by the compound. The sup-
pressions of both NF-κB (Figure 1B) and MAPK (Figure
1C) pathway activation were demonstrated in curcumin.
IN VIVO STUDIES
There have been a few studies to discuss anti-H. pylori and
anti-H. pylori induced gastric inflammation (or gastritis)
activities of natural products in animals. As aforemen-
tioned[85], tea catechins had anti-H. pylori activity (MIC:
WJG|www.wjgnet.com 10377
8-256 μg/mL) in vitro. The product was given in diet
(0.5%) for 2 wk to Mongolian gerbils. The H. pylori colo-
nization reduced by 10%-36% and gastric mucosal injury
significantly decreased[85]. Both kaempferol and trypt-
anthrin showed anti-H. pylori activity[66,109]. A mixture of
kaempferol and tryptanthrin at 5.0 mg/bw of treatment
dose was orally administered to Mongolian gerbils twice
a day for 10 d. The viable counts of H. pylori in the stom-
ach significantly decreased[132]. Quercetin, a flavonoid, is
widely present in fruits and vegetables. H. pylori-infected
guinea pigs were orally given quercetin at 200 mg/kgbw
per day, which significantly decreased neutrophil leuko-
cyte infiltration, H. pylori colonization, and lipid peroxide
concentration in the pyloric antrum[133]. The carotenoid-
rich acetone extract of Chlorococcum sp. (a microalgae) was
orally given to H. pylori-infected BALB/c mice at 100
mg/kgbw per day. The algae meal significantly decreased
H. pylori density in the stomach and INF-γ and IL-4
levels in splenocytes; the H. pylori-induced inflammation
in BALB/c mice was effectively inhibited[134]. A green
tea product containing 30.7% epigallocatechin gallate,
17.0% epigallocatechin, 6.4% epicatechin gallate, 5.7%
gallocatechin, 4.2% gallocatechin gallate, 4.1% epicat-
echin, and 1.1% catechin was given in drinking water at
500-2000 ppm doses for 6 wk to H. pylori-infected Mon-
golian gerbils. Gastritis and the prevalence of H. pylori in
the Mongolian gerbils were significantly suppressed in a
dose-dependent manner[135]. Additionally, a garlic ethanol
aqueous extract was given at 1%-4% of dosages in a diet
to H. pylori-infected Mongolian gerbils. The garlic extract
significantly decreased hemorrhagic spots in the glandular
stomach and gastritis scores as well as decreased stomach
weight, which might be useful as an agent for prevention
of H. pylori-induced gastritis[136]. In a 4-wk short-term
H. pylori infection model, H. pylori-infected C57BL6/J
mice were orally administered apple peel polyphenol (150
and 300 mg/kgbw per day). The treatment significantly
decreased H. pylori colonization, gastritis scores, and
malondialdehyde levels in the animals[137]. The Thai medi-
cines finger-root and turmeric rhizome with 95% ethanol
extracts were given to H. pylori-infected Mongolian ger-
bils in a basal diet at 100 mg/kgbw per day. The finger-
root extract effectively decreased mucosal/submucosal
chronic and acute inflammation scores for those Mon-
golian gerbils. The turmeric extract only reduced chronic
inflammation scores, without anti-acute inflammation ef-
fects[138]. In 32-wk and 52-wk animal tests, apigenin treat-
ments (30-60 mg/kgbw per day) effectively decreased H.
pylori colonization, atrophic gastritis, and dysplasia/gas-
tric cancer rates in H. pylori-infected Mongolian gerbils.
Apigenin has the remarkable ability to inhibit H. pylori-
induced gastric cancer progression as well as possessing
potent anti-gastric cancer activity[139].
CONCLUSION
H. pylori infection may result in severe gastric inflam-
mation and gastric cancer. CagA is a key virulent factor,
August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases
which initiates host cells’ NF-κB, MAPK, and SHP-2/
ERK pathways to transcribe and translate inflammatory
factors (COX-2, ICAM-1, iNOS, ROS) and proinflam-
matory cytokines (IL-6, IL-8, INF-γ, TNF-α). Overpro-
duction of those substances cause extensive infected-site
inflammation and then progress to superficial gastritis,
atrophic gastritis, and finally gastric cancer.
Numerous medicinal plant products including plant
extracts, partial purified fractions, and isolated com-
pounds were reported for their anti-H. pylori activity. A
few of them exhibited strong anti-H. pylori activity, being
almost equal to clinical antibiotics. In animals, few plant
products had anti-H. pylori effects which effectively de-
creased H. pylori colonization in the stomach. H. pylori-
induced atrophic gastritis is a critical point to progress
to gastric cancer. Some plant products, including isolated
compounds and plant formulas, significantly decreased
such gastric inflammation and injury, and even inhibited
gastric cancer progression.
H. pylori eradication with antibiotic regimens has a
limitation mostly due to antibiotic resistance. Medicinal
plant compounds and other natural products provide
another choice or opportunity to eradicate H. pylori infec-
tion. Medicinal plant compounds may also provide effec-
tive way to reduce H. pylori-induced gastric inflammation
and even gastric cancer. However, potential cytotoxicity
and adverse side effects might present from those medic-
inal plant products. Further relevant cytotoxicity studies
both in vitro and in vivo will be required. Further evalua-
tion of pharmacokin-etics for those products in animals
will be also required.
REFERENCES
1 Warren JR, Marshall BJ. Unidentified curved bacilli on
gastric epithelium in active chronic gastritis. Lancet 1983; 1:
1273-1275 [PMID: 6134060]
2 Taylor D, Parsonneet, J. Infections of the gastrointestinal
tract. In: Infection of the gastrointestinal tract. New York:
Ravan Press, 1995: 551-563
3 World Health Organization. IARC monographs on the
evaluation of carcinogenic risks to humans, Vol 61. Geneva:
World Health Organization, 1994: 177-240
4 Covacci A, Telford JL, Del Giudice G, Parsonnet J, Rappuoli
R. Helicobacter pylori virulence and genetic geography. Sci-
ence 1999; 284: 1328-1333 [PMID: 10334982]
5 Dundon WG, de Bernard M, Montecucco C. Virulence fac-
tors of Helicobacter pylori. Int J Med Microbiol 2001; 290:
647-658 [PMID: 11310443 DOI: 10.3109/00365529109098222]
6 Mobley HLT, Mendz GL, Hazell SL. Helicobacter pylori.
Washington (DC): ASM Press, 2001: Pp. 471-498
7 Yamaoka Y. Mechanisms of disease: Helicobacter pylori vir-
ulence factors. Nat Rev Gastroenterol Hepatol 2010; 7: 629-641
[PMID: 20938460 DOI: 10.1038/nrgastro.2010.154]
8 Aguilar GR, Ayala G, Fierros-Zárate G. Helicobacter py-
lori: recent advances in the study of its pathogenicity and
prevention. Salud Publica Mex 2001; 43: 237-247 [PMID:
11452701 DOI: 10.1590/S0036-36342001000300010]
9 Atherton JC. H. pylori virulence factors. Br Med Bull 1998;
54: 105-120 [PMID: 9604436 DOI: 10.1093/oxfordjournals.
bmb.a011662]
10 Blanke SR. Micro-managing the executioner: pathogen
targeting of mitochondria. Trends Microbiol 2005; 13: 64-71
WJG|www.wjgnet.com 10378
[PMID: 15680765 DOI: 10.1016/j.tim.2004.12.007]
11 Boquet P, Ricci V. Intoxication strategy of Helicobacter py-
lori VacA toxin. Trends Microbiol 2012; 20: 165-174 [PMID:
22364673 DOI: 10.1016/j.tim.2012.01.008]
12 Polk DB, Peek RM. Helicobacter pylori: gastric cancer and
beyond. Nat Rev Cancer 2010; 10: 403-414 [PMID: 20495574
DOI: 10.1038/nrc2857]
13 Wada A, Yamasaki E, Hirayama T. Helicobacter pylori
vacuolating cytotoxin, VacA, is responsible for gastric ul-
ceration. J Biochem 2004; 136: 741-746 [PMID: 15671482 DOI:
10.1093/jb/mvh181]
14 Kim IJ, Blanke SR. Remodeling the host environment: mod-
ulation of the gastric epithelium by the Helicobacter pylori
vacuolating toxin (VacA). Front Cell Infect Microbiol 2012; 2:
37 [PMID: 22919629 DOI: 10.3389/fcimb.2012.00037]
15 Palframan SL, Kwok T, Gabriel K. Vacuolating cytotoxin
A (VacA), a key toxin for Helicobacter pylori pathogenesis.
Front Cell Infect Microbiol 2012; 2: 92 [PMID: 22919683 DOI:
10.3389/fcimb.2012.00092]
16 Kuck D, Kolmerer B, Iking-Konert C, Krammer PH, Strem-
mel W, Rudi J. Vacuolating cytotoxin of Helicobacter pylori
induces apoptosis in the human gastric epithelial cell line
AGS. Infect Immun 2001; 69: 5080-5087 [PMID: 11447189
DOI: 10.1128/IAI.69.8.5080-5087.2001]
17 Cover TL, Krishna US, Israel DA, Peek RM. Induction
of gastric epithelial cell apoptosis by Helicobacter pylori
vacuolating cytotoxin. Cancer Res 2003; 63: 951-957 [PMID:
12615708]
18 Mimuro H, Suzuki T, Nagai S, Rieder G, Suzuki M, Nagai
T, Fujita Y, Nagamatsu K, Ishijima N, Koyasu S, Haas R, Sa-
sakawa C. Helicobacter pylori dampens gut epithelial self-
renewal by inhibiting apoptosis, a bacterial strategy to en-
hance colonization of the stomach. Cell Host Microbe 2007; 2:
250-263 [PMID: 18005743 DOI: 10.1016/j.chom.2007.09.005]
19 Jones KR, Whitmire JM, Merrell DS. A tale of two toxins:
Helicobacter pylori CagA and VacA modulate host path-
ways that impact disease. Front Microbiol 2010; 1: 115 [PMID:
21687723 DOI: 10.3389/fmicb.2010.00115]
20 Wu J, Xu S, Zhu Y. Helicobacter pylori CagA: a critical
destroyer of the gastric epithelial barrier. Dig Dis Sci 2013;
58: 1830-1837 [PMID: 23423500 DOI: 10.1007/s10620-013-
2589-x]
21 Hatakeyama M, Higashi H. Helicobacter pylori CagA: a new
paradigm for bacterial carcinogenesis. Cancer Sci 2005; 96:
835-843 [PMID: 16367902 DOI: 10.1111/j.1349-7006.2005.00130.
x]
22 Correa P. Human gastric carcinogenesis: a multistep and
multifactorial process--First American Cancer Society Award
Lecture on Cancer Epidemiology and Prevention. Cancer Res
1992; 52: 6735-6740 [PMID: 1458460]
23 Fox JG, Wang TC. Helicobacter pylori--not a good bug after
all. N Engl J Med 2001; 345: 829-832 [PMID: 11556306 DOI:
10.1056/NEJM200109133451111]
24 Fox JG, Wang TC. Inflammation, atrophy, and gastric
cancer. J Clin Invest 2007; 117: 60-69 [PMID: 17200707 DOI:
10.1172/JCI30111]
25 Jobin C, Sartor RB. The I kappa B/NF-kappa B system: a key
determinant of mucosalinflammation and protection. Am J
Physiol Cell Physiol 2000; 278: C451-C462 [PMID: 10712233]
26 Jacobs MD, Harrison SC. Structure of an IkappaBalpha/
NF-kappaB complex. Cell 1998; 95: 749-758 [PMID: 9865693
DOI: 10.1016/s0092-8674(00)81698-0]
27 Naito Y, Yoshikawa T. Molecular and cellular mechanisms
involved in Helicobacter pylori-induced inflammation and
oxidative stress. Free Radic Biol Med 2002; 33: 323-336 [PMID:
12126754]
28 Crantree JE, Naumann M. Epithelial cell signaling in Heli-
cobacter pylori infection. Curr Signal Transduct Ther 2006; 1:
53-56 [DOI: 10.2174/157436206775269253]
29 Peek RM, Fiske C, Wilson KT. Role of innate immunity in
August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases
Helicobacter pylori-induced gastric malignancy. Physiol
Rev 2010; 90: 831-858 [PMID: 20664074 DOI: 10.1152/phys-
rev.00039.2009]
30 Bonizzi G, Karin M. The two NF-kappaB activation path-
ways and their role in innate and adaptive immunity. Trends
Immunol 2004; 25: 280-288 [PMID: 15145317 DOI: 10.1016/
j.it.2004.03.008]
31 Lee JS, Paek NS, Kwon OS, Hahm KB. Anti-inflammatory
actions of probiotics through activating suppressor of cyto-
kine signaling (SOCS) expression and signaling in Helico-
bacter pylori infection: a novel mechanism. J Gastroenterol
Hepatol 2010; 25: 194-202 [PMID: 20136974 DOI: 10.1111/
j.1440-1746.2009.06127.x]
32 Allison CC, Kufer TA, Kremmer E, Kaparakis M, Ferrero
RL. Helicobacter pylori induces MAPK phosphorylation
and AP-1 activation via a NOD1-dependent mechanism.
J Immunol 2009; 183: 8099-8109 [PMID: 20007577 DOI:
10.4049/jimmunol.0900664]
33 Montecucco C, Rappuoli R. Living dangerously: how Helico-
bacter pylori survives in the human stomach. Nat Rev Mol Cell
Biol 2001; 2: 457-466 [PMID: 11389469 DOI: 10.1038/35073084]
34 Cho SO, Lim JW, Kim KH, Kim H. Involvement of Ras and
AP-1 in Helicobacter pylori-induced expression of COX-2
and iNOS in gastric epithelial AGS cells. Dig Dis Sci 2010;
55: 988-996 [PMID: 19495976 DOI: 10.1007/s10620-009-
0828-y]
35 Lambeth JD. NOX enzymes and the biology of reactive
oxygen. Nat Rev Immunol 2004; 4: 181-189 [PMID: 15039755
DOI: 10.1038/nri1312]
36 Teshima S, Rokutan K, Nikawa T, Kishi K. Guinea pig
gastric mucosal cells produce abundant superoxide anion
through an NADPH oxidase-like system. Gastroenterol-
ogy 1998; 115: 1186-1196 [PMID: 9797374 DOI: 10.1016/
s0016-5085(98)70090-3]
37 Teshima S, Kutsumi H, Kawahara T, Kishi K, Rokutan K.
Regulation of growth and apoptosis of cultured guinea pig
gastric mucosal cells by mitogenic oxidase 1. Am J Physiol
Gastrointest Liver Physiol 2000; 279: G1169-G1176 [PMID:
11093939]
38 Babior BM, Lambeth JD, Nauseef W. The neutrophil
NADPH oxidase. Arch Biochem Biophys 2002; 397: 342-344
[PMID: 11795892 DOI: 10.1006/abbi.2001.2642]
39 Morena M, Cristol JP, Senécal L, Leray-Moragues H, Krieter
D, Canaud B. Oxidative stress in hemodialysis patients: is
NADPH oxidase complex the culprit? Kidney Int Suppl 2002;
(80): 109-114 [PMID: 11982824 DOI: 10.1046/j.1523-1755.61.
s80.1.x]
40 Kroemer G, Dallaporta B, Resche-Rigon M. The mitochon-
drial death/life regulator in apoptosis and necrosis. Annu
Rev Physiol 1998; 60: 619-642 [PMID: 9558479 DOI: 10.1146/
annurev.physiol.60.1.619]
41 Fera MT, Giannone M, Pallio S, Tortora A, Blandino G,
Carbone M. Antimicrobial activity and postantibiotic effect
of flurithromycin against Helicobacter pylori strains. Int J
Antimicrob Agents 2001; 17: 151-154 [PMID: 11165121 DOI:
10.1016/S0924-8579(00)00315-0]
42 Boyanova L. Comparative evaluation of two methods for
testing metronidazole susceptibility of Helicobacter pylori
in routine practice. Diagn Microbiol Infect Dis 1999; 35: 33-36
[PMID: 10529879 DOI: 10.1016/S0732-8893(99)00039-5]
43 Park JB, Imamura L, Kobashi K. Kinetic studies of Helico-
bacter pylori urease inhibition by a novel proton pump in-
hibitor, rabeprazole. Biol Pharm Bull 1996; 19: 182-187 [PMID:
8850302 DOI: 10.1248/bpb.19.182]
44 Tsuchiya M, Imamura L, Park JB, Kobashi K. Helicobacter
pylori urease inhibition by rabeprazole, a proton pump in-
hibitor. Biol Pharm Bull 1995; 18: 1053-1056 [PMID: 8535394
DOI: 10.1248/bpb.18.1053]
45 Susan M, Mou MD. The relationship between Helicobacter
infection and peptic ulcer disease. Prim Care Update Ob/Gyns
WJG|www.wjgnet.com 10379
1998; 5: 229-232 [DOI: 10.1016/s1068-607x(98)00155-3]
46 Sorba G, Bertinaria M, Di Stilo A, Gasco A, Scaltrito MM,
Brenciaglia MI, Dubini F. Anti-Helicobacter pylori agents
endowed with H2-antagonist properties. Bioorg Med Chem
Lett 2001; 11: 403-406 [PMID: 11212121 DOI: 10.1016/s0960-
894x(00)00671-5]
47 Midolo PD, Norton A, von Itzstein M, Lambert JR. Novel
bismuth compounds have in vitro activity against Helico-
bacter pylori. FEMS Microbiol Lett 1997; 157: 229-232 [PMID:
9435101 DOI: 10.1111/j.1574-6968.1997.tb12777.x]
48 Worrel JA, Stoner SC. Eradication of Helicobacter py-
lori. Med Update Psychiat 1998; 4: 99-104 [DOI: 10.1016/
s1082-7579(98)00012-0]
49 Ferrero M, Ducóns JA, Sicilia B, Santolaria S, Sierra E, Gomol-
lón F. Factors affecting the variation in antibiotic resistance
of Helicobacter pylori over a 3-year period. Int J Antimicrob
Agents 2000; 16: 245-248 [PMID: 11091043 DOI: 10.1016/
s0924-8579(00)00205-3]
50 Glupczynski Y, Mégraud F, Lopez-Brea M, Andersen LP. Eu-
ropean multicentre survey of in vitro antimicrobial resistance
in Helicobacter pylori. Eur J Clin Microbiol Infect Dis 2001; 20:
820-823 [PMID: 11783701 DOI: 10.1007/s100960100611]
51 Hirschl A, Andersen LP, Glupczynski Y. Surveillance
of Helicobacter pylori resistance to antibiotics in Europe
2008-2009. Gastroenterology 2009; 140: S312 [DOI: 10.1016/
S0016-5085(11)61257-2]
52 Wang YC, Wu DC, Liao JJ, Wu CH, Li WY, Weng BC. In vi-
tro activity of Impatiens balsamina L. against multiple anti-
biotic-resistant Helicobacter pylori. Am J Chin Med 2009; 37:
713-722 [PMID: 19655409 DOI: 10.1142/S0192415X09007181]
53 Castillo-Juárez I, González V, Jaime-Aguilar H, Martínez G,
Linares E, Bye R, Romero I. Anti-Helicobacter pylori activity
of plants used in Mexican traditional medicine for gastroin-
testinal disorders. J Ethnopharmacol 2009; 122: 402-405 [PMID:
19162157 DOI: 10.1016/j.jep.2008.12.021]
54 Mahady GB, Pendland SL, Stoia A, Chadwick LR. In vitro
susceptibility of Helicobacter pylori to isoquinoline alka-
loids from Sanguinaria canadensis and Hydrastis canaden-
sis. Phytother Res 2003; 17: 217-221 [PMID: 12672149 DOI:
10.1002/ptr.1776]
55 Zaidi SF, Yamada K, Kadowaki M, Usmanghani K, Sugi-
yama T. Bactericidal activity of medicinal plants, employed
for the treatment of gastrointestinal ailments, against Heli-
cobacter pylori. J Ethnopharmacol 2009; 121: 286-291 [PMID:
19041711 DOI: 10.1016/j.jep.2008.11.001]
56 Li Y, Xu C, Zhang Q, Liu JY, Tan RX. In vitro anti-Helico-
bacter pylori action of 30 Chinese herbal medicines used to
treat ulcer diseases. J Ethnopharmacol 2005; 98: 329-333 [PMID:
15814268 DOI: 10.1016/j.jep.2005.01.020]
57 Ohsaki A, Takashima J, Chiba N, Kawamura M. Microanaly-
sis of a selective potent anti-Helicobacter pylori compound in
a Brazilian medicinal plant, Myroxylon peruiferum and the
activity of analogues. Bioorg Med Chem Lett 1999; 9: 1109-1112
[PMID: 10328294 DOI: 10.1016/S0960-894X(99)00141-9]
58 Gadhi CA, Benharref A, Jana M, Lozniewski A. Anti-Heli-
cobacter pylori activity of Aristolochia paucinervis Pomel
extracts. J Ethnopharmacol 2001; 75: 203-205 [PMID: 11297852
DOI: 10.1016/S0378-8741(01)00184-2]
59 Yeşilada E, Gürbüz I, Shibata H. Screening of Turkish anti-
ulcerogenic folk remedies for anti-Helicobacter pylori activ-
ity. J Ethnopharmacol 1999; 66: 289-293 [PMID: 10473175 DOI:
10.1016/S0378-8741(98)00219-0]
60 Stege PW, Davicino RC, Vega AE, Casali YA, Correa S,
Micalizzi B. Antimicrobial activity of aqueous extracts of
Larrea divaricata Cav (jarilla) against Helicobacter pylori.
Phytomedicine 2006; 13: 724-727 [PMID: 17085295 DOI:
10.1016/j.phymed.2005.06.008]
61 Amin M, Anwar F, Naz F, Mehmood T, Saari N. Anti-
Helicobacter pylori and urease inhibition activities of some
traditional medicinal plants. Molecules 2013; 18: 2135-2149
August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases
[PMID: 23434867 DOI: 10.3390/molecules18022135]
62 Nostro A, Cellini L, Di Bartolomeo S, Cannatelli MA, Di
Campli E, Procopio F, Grande R, Marzio L, Alonzo V. Ef-
fects of combining extracts (from propolis or Zingiber
officinale) with clarithromycin on Helicobacter pylori. Phy-
tother Res 2006; 20: 187-190 [PMID: 16521108 DOI: 10.1002/
ptr.1830]
63 Chinniah A, Mohapatra S, Goswami S, Mahapatra A, Kar
SK, Mallavadhani UV, Das PK. On the potential of Tephro-
sia purpurea as anti-Helicobacter pylori agent. J Ethnophar-
macol 2009; 124: 642-645 [PMID: 19467317 DOI: 10.1016/
j.jep.2009.05.016]
64 Silva O, Viegas S, de Mello-Sampayo C, Costa MJ, Serrano
R, Cabrita J, Gomes ET. Anti-Helicobacter pylori activity
of Terminalia macroptera root. Fitoterapia 2012; 83: 872-876
[PMID: 22465506 DOI: 10.1016/j.fitote.2012.03.019]
65 Malekzadeh F, Ehsanifar H, Shahamat M, Levin M, Colwell
RR. Antibacterial activity of black myrobalan (Terminalia
chebula Retz) against Helicobacter pylori. Int J Antimicrob
Agents 2001; 18: 85-88 [PMID: 11463533 DOI: 10.1016/
S0924-8579(01)00352-1]
66 Martini S, D’Addario C, Colacevich A, Focardi S, Borghini
F, Santucci A, Figura N, Rossi C. Antimicrobial activity
against Helicobacter pylori strains and antioxidant proper-
ties of blackberry leaves (Rubus ulmifolius) and isolated
compounds. Int J Antimicrob Agents 2009; 34: 50-59 [PMID:
19386474 DOI: 10.1016/j.ijantimicag.2009.01.010]
67 Castillo-Juárez I, Rivero-Cruz F, Celis H, Romero I. Anti-
Helicobacter pylori activity of anacardic acids from Amphi-
pterygium adstringens. J Ethnopharmacol 2007; 114: 72-77
[PMID: 17768020 DOI: 10.1016/j.jep.2007.07.022]
68 Ndip RN, Aj o n g l e f a c A N , M b u l l a h S M , T a n i h N F ,
Akoachere JTK, Ndip LM, Luma HN, Wirmum C, Ngwa F,
Efange SMN. In vitro anti-Helicobacter pylori activity of Ly-
copodium cernuum (Linn) Pic. Serm. Afr J Biotechnol 2008; 7:
3989-3994 [DOI: 10.5897/AJB08.595]
69 Ndip RN, Malange Tarkang AE, Mbullah SM, Luma HN,
Malongue A, Ndip LM, Nyongbela K, Wirmum C, Efange
SM. In vitro anti-Helicobacter pylori activity of extracts of
selected medicinal plants from North West Cameroon. J
Ethnopharmacol 2007; 114: 452-457 [PMID: 17913416 DOI:
10.1016/j.jep.2007.08.037]
70 Njume C, Afolayan AJ, Ndip RN. Preliminary phytochemi-
cal screening and in vitro anti-Helicobacter pylori activity
of acetone and aqueous extracts of the stem bark of Sclero-
carya birrea (Anacardiaceae). Arch Med Res 2011; 42: 252-257
[PMID: 21722823 DOI: 10.1016/j.arcmed.2011.04.009]
71 Germanò MP, Sanogo R, Guglielmo M, De Pasquale R, Cri-
safi G, Bisignano G. Effects of Pteleopsis suberosa extracts
on experimental gastric ulcers and Helicobacter pylori
growth. J Ethnopharmacol 1998; 59: 167-172 [PMID: 9507900
DOI: 10.1016/S0378-8741(97)00109-8]
72 Nostro A, Cellini L, Di Bartolomeo S, Di Campli E, Grande
R, Cannatelli MA, Marzio L, Alonzo V. Antibacterial effect
of plant extracts against Helicobacter pylori. Phytother Res
2005; 19: 198-202 [PMID: 15934015]
73 Cellini L, Di Campli E, Masulli M, Di Bartolomeo S, Allocati
N. Inhibition of Helicobacter pylori by garlic extract (Allium
sativum). FEMS Immunol Med Microbiol 1996; 13: 273-277
[PMID: 8739190 DOI: 10.1016/0928-8244(95)00120-4]
74 Cwikla C, Schmidt K, Matthias A, Bone KM, Lehmann R,
Tiralongo E. Investigations into the antibacterial activities
of phytotherapeutics against Helicobacter pylori and Cam-
pylobacter jejuni. Phytother Res 2010; 24: 649-656 [PMID:
19653313 DOI: 10.1002/ptr.2933]
75 Cogo LL, Monteiro CL, Miguel MD, Miguel OG, Cunico
MM, Ribeiro ML, de Camargo ER, Kussen GM, Nogueira
Kda S, Costa LM. Anti-Helicobacter pylori activity of plant
extracts traditionally used for the treatment of gastrointes-
tinal disorders. Braz J Microbiol 2010; 41: 304-309 [PMID:
WJG|www.wjgnet.com
24031496 DOI: 10.1590/S1517-83822010000200007]
76 Adeniyi BA, Anyiam FM. In vitro anti-Helicobacter pylori
potential of methanol extract of Allium ascalonicum Linn.
(Liliaceae) leaf: susceptibility and effect on urease activ-
ity. Phytother Res 2004; 18: 358-361 [PMID: 15173992 DOI:
10.1002/ptr.1265]
77 Voravuthikunchai SP, Mitchell H. Inhibitory and killing
activities of medicinal plants against multiple antibiotic-
resistant Helicobacter pylori. J Health Sci 2008; 54: 81-88 [DOI:
10.1248/jhs.54.81]
78 Stamatis G, Kyriazopoulos P, Golegou S, Basayiannis A,
Skaltsas S, Skaltsa H. In vitro anti-Helicobacter pylori activity
of Greek herbal medicines. J Ethnopharmacol 2003; 88: 175-179
[PMID: 12963139 DOI: 10.1016/S0378-8741(03)00217-4]
79 Wang YC, Huang TL. Anti-Helicobacter pylori activity of
Plumbago zeylanica L. FEMS Immunol Med Microbiol 2005; 43:
407-412 [PMID: 15708315 DOI: 10.1016/j.femsim.2004.10.015]
80 Wang YC, Huang TL. Screening of anti-Helicobacter pylori
herbs deriving from Taiwanese folk medicinal plants. FEMS
Immunol Med Microbiol 2005; 43: 295-300 [PMID: 15681161
DOI: 10.1016/j.femsim.2004.09.008]
81 Ohno T, Kita M, Yamaoka Y, Imamura S, Yamamoto T,
Mitsufuji S, Kodama T, Kashima K, Imanishi J. Antimicro-
bial activity of essential oils against Helicobacter pylori.
Helicobacter 2003; 8: 207-215 [PMID: 12752733 DOI: 10.1046/
j.1523-5378.2003.00146.x]
82 Epifano F, Menghini L, Pagiotti R, Angelini P, Genovese
S, Curini M. In vitro inhibitory activity of boropinic acid
against Helicobacter pylori. Bioorg Med Chem Lett 2006; 16:
5523-5525 [PMID: 16945527 DOI: 10.1016/j.bmcl.2006.08.043]
83 Zhang XQ, Gu HM, Li XZ, Xu ZN, Chen YS, Li Y. Anti-
Helicobacter pylori compounds from the ethanol extracts
of Geranium wilfordii. J Ethnopharmacol 2013; 147: 204-207
[PMID: 23500884 DOI: 10.1016/j.jep.2013.02.032]
84 Rüegg T, Calderón AI, Queiroz EF, Solís PN, Marston
A, Rivas F, Ortega-Barría E, Hostettmann K, Gupta MP.
3-Farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter
pylori compound from Piper multiplinervium. J Ethnophar-
macol 2006; 103: 461-467 [PMID: 16266794 DOI: 10.1016/
j.jep.2005.09.014]
85 Mabe K, Yamada M, Oguni I, Takahashi T. In vitro and in
vivo activities of tea catechins against Helicobacter pylori.
Antimicrob Agents Chemother 1999; 43: 1788-1791 [PMID:
10390246 DOI: 10.1111/j.1550-7408.2002.]
86 Bae EA, Han MJ, Kim NJ, Kim DH. Anti-Helicobacter py-
lori activity of herbal medicines. Biol Pharm Bull 1998; 21:
990-992 [PMID: 9781854]
87 Yin S, Fan CQ, Yue JM. Psoracorylifols A-E, five novel com-
pounds with activity against Helicobacter pylori from seeds
of Psoralea corylofolia. Tetrahedron 2006; 62: 2569-2575 [DOI:
10.1016/j.tet.2005.12.041]
88 Paulo L, Oleastro M, Gallardo E, Queiroz JA, Domingues F.
Anti-Helicobacter pylori and urease inhibitory activities of
resveratrol and red wine. Food Res Intl 2011; 44: 964-969 [DOI:
10.1016/j.foodres.2011.02.017]
89 Mahady GB, Matsuura H, Pendland SL. Allixin, a phyto-
alexin from garlic, inhibits the growth of Helicobacter py-
lori in vitro. Am J Gastroenterol 2001; 96: 3454-3455 [PMID:
11774979 DOI: 10.1111/j.1572-0241.2001.05351.x]
90 Ngan LT, Moon JK, Shibamoto T, Ahn YJ. Growth-inhib-
iting, bactericidal, and urease inhibitory effects of Paeonia
lactiflora root constituents and related compounds on anti-
biotic-susceptible and -resistant strains of Helicobacter py-
lori. J Agric Food Chem 2012; 60: 9062-9073 [PMID: 22891951
DOI: 10.1021/jf3035034]
91 Banskota AH, Tezuka Y, Adnyana IK, Ishii E, Midorikawa
K, Matsushige K, Kadota S. Hepatoprotective and anti-
Helicobacter pylori activities of constituents from Brazilian
propolis. Phytomedicine 2001; 8: 16-23 [PMID: 11292234 DOI:
10.1078/0944-7113-00004]
10380 August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases
92 Konstantinopoulou M, Karioti A, Skaltsas S, Skaltsa H.
Sesquiterpene lactones from Anthemis altissima and their
anti-Helicobacter pylori activity. J Nat Prod 2003; 66: 699-702
[PMID: 12762812 DOI: 10.1021/up020472m]
93 Ustün O, Ozçelik B, Akyön Y, Abbasoglu U, Yesilada E. Fla-
vonoids with anti-Helicobacter pylori activity from Cistus
laurifolius leaves. J Ethnopharmacol 2006; 108: 457-461 [PMID:
16870372 DOI: 10.1016/j.jep.2006.06.001]
94 Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura
T. Anti-Helicobacter pylori flavonoids from licorice extract.
Life Sci 2002; 71: 1449-1463 [PMID: 12127165 DOI: 10.1016/
S0024-3205(02)01864-7]
95 Wang YC, Li WY, Wu DC, Wang JJ, Wu CH, Liao JJ, Lin
CK. In vitro activity of 2-methoxy-1,4-naphthoquinone and
stigmasta-7,22-diene-3β-ol from impatiens balsamina L.
against multiple antibiotic-resistant Helicobacter pylori. Evid
Based Complement Alternat Med 2011; 2011: 704721 [PMID:
19773391 DOI: 10.1093/ecam/nep147]
96 Park BS, Lee HK, Lee SE, Piao XL, Takeoka GR, Wong RY,
Ahn YJ, Kim JH. Antibacterial activity of Tabebuia impetigi-
nosa Martius ex DC (Taheebo) against Helicobacter pylori.
J Ethnopharmacol 2006; 105: 255-262 [PMID: 16359837 DOI:
10.1016/j.jep.2005.11.005]
97 Inatsu S, Ohsaki A, Nagata K. Idebenone acts against growth
of Helicobacter pylori by inhibiting its respiration. Antimicrob
Agents Chemother 2006; 50: 2237-2239 [PMID: 16723594 DOI:
10.1128/AAC.01118-05]
98 Wang HH, Chung JG. Emodin-induced inhibition of growth
and DNA damage in the Helicobacter pylori. Curr Microbiol
1997; 35: 262-266 [PMID: 9462956 DOI: 10.1007/s002849900250]
99 Basile A, Sorbo S, Spadaro V, Bruno M, Maggio A, Faraone
N, Rosselli S. Antimicrobial and antioxidant activities of
coumarins from the roots of Ferulago campestris (Apiaceae).
Molecules 2009; 14: 939-952 [PMID: 19255552 DOI: 10.3390/
molecules14030939]
100 Jadhav SG, Meshram RJ, Gond DS, Gacche RN. Inhibition
of growth of Helicobacter pylori and its urease by couma-
rin derivatives: Molecular docking analysis. J Pharmacy Res
2013; 7: 705-711 [DOI: 10.1016/j.jopr.2013.09.002]
101 Kawase M, Tanaka T, Sohara Y, Tani S, Sakagami H, Hauer
H, Chatterjee SS. Structural requirements of hydroxylated
coumarins for in vitro anti-Helicobacter pylori activity. In
Vivo 2003; 17: 509-512 [PMID: 14598616]
102 De Leo M, De Tommasi N, Sanogo R, D’Angelo V, Ger-
manò MP, Bisignano G, Braca A. Triterpenoid saponins
from Pteleopsis suberosa stem bark. Phytochemistry 2006; 67:
2623-2629 [PMID: 16950485]
103 Kadota S, Basnet P, Ishii E, Tamura T, Namba T. Antibacte-
rial activity of trichorabdal A from Rabdosia trichocarpa
against Helicobacter pylori. Zentralbl Bakteriol 1997; 286:
63-67 [PMID: 9241802 DOI: 10.1016/s0934-8840(97)80076-x]
104 Ochi T, Shibata H, Higuti T, Kodama KH, Kusumi T, Takai-
shi Y. Anti-Helicobacter pylori compounds from Santalum
album. J Nat Prod 2005; 68: 819-824 [PMID: 15974602 DOI:
10.1021/np040188q]
105 Koga T, Kawada H, Utsui Y, Domon H, Ishii C, Yasuda H.
In-vitro and in-vivo antibacterial activity of plaunotol, a
cytoprotective antiulcer agent, against Helicobacter pylori. J
Antimicrob Chemother 1996; 37: 919-929 [PMID: 8737142 DOI:
10.1093/jac/37.5.919]
106 Njume C, Afolayan AJ, Green E, Ndip RN. Volatile com-
pounds in the stem bark of Sclerocarya birrea (Anacardia-
ceae) possess antimicrobial activity against drug-resistant
strains of Helicobacter pylori. Int J Antimicrob Agents 2011;
38: 319-324 [PMID: 21752604 DOI: 10.16/j.ijantimicag.2011.0
5.002]
107 Hamasaki N, Ishii E, Tominaga K, Tezuka Y, Nagaoka T,
Kadota S, Kuroki T, Yano I. Highly selective antibacterial
activity of novel alkyl quinolone alkaloids from a Chinese
herbal medicine, Gosyuyu (Wu-Chu-Yu), against Helico-
WJG|www.wjgnet.com 10381
bacter pylori in vitro. Microbiol Immunol 2000; 44: 9-15 [PMID:
10711594]
108 Hashimoto T, Agr H, Chaen H, Fukuda S, Kurimoto M.
Isolation and identification of anti-Helicobacter pylori com-
pounds from Polygonum tinctorium Lour. Nat Med 1999; 53:
27-31
109 O'Gara EA, Hill DJ, Maslin DJ. Activities of garlic oil, garlic
powder, and their diallyl constituents against Helicobacter
pylori. Appl Environ Microbiol 2000; 66: 2269-2273 [PMID:
10788416 DOI: 10.1128/AEM.66.5.2269-2273.2000]
110 Tabak M, Armon R, Rosenblat G, Stermer E, Neeman I.
Diverse effects of ascorbic acid and palmitoyl ascorbate on
Helicobacter pylori survival and growth. FEMS Microbiol
Lett 2003; 224: 247-253 [PMID: 12892889 DOI: 10.1016/
S0378-1097(03)00439-7]
111 Sun CQ, O’Connor CJ, Roberton AM. Antibacterial actions
of fatty acids and monoglycerides against Helicobacter
pylori. FEMS Immunol Med Microbiol 2003; 36: 9-17 [PMID:
12727360 DOI: 10.1016/S0928-8244(03)00008-7]
112 Cowan MM. Plant products as antimicrobial agents. Clin
Microbiol Rev 1999; 12: 564-582 [PMID: 10515903]
113 Lin YT, Kwon YI, Labbe RG, Shetty K. Inhibition of Heli-
cobacter pylori and associated urease by oregano and cran-
berry phytochemical synergies. Appl Environ Microbiol 2005;
71: 8558-8564 [PMID: 16332847]
114 Souza Mdo C, Beserra AM, Martins DC, Real VV, Santos
RA, Rao VS, Silva RM, Martins DT. In vitro and in vivo
anti-Helicobacter pylori activity of Calophyllum brasiliense
Camb. J Ethnopharmacol 2009; 123: 452-458 [PMID: 19501278
DOI: 10.1016/j.jep.2009.03.030]
115 O'Mahony R, Al-Khtheeri H, Weerasekera D, Fernando N,
Vaira D, Holton J, Basset C. Bactericidal and anti-adhesive
properties of culinary and medicinal plants against Helico-
bacter pylori. World J Gastroenterol 2005; 11: 7499-7507 [PMID:
16437723]
116 Wittschier N, Faller G, Hensel A. Aqueous extracts and
polysaccharides from liquorice roots (Glycyrrhiza glabra
L.) inhibit adhesion of Helicobacter pylori to human gas-
tric mucosa. J Ethnopharmacol 2009; 125: 218-223 [PMID:
19607905 DOI: 10.1016/j.jep.2009.07.009]
117 Wittschier N, Faller G, Hensel A. An extract of Pelargonium
sidoides (EPs 7630) inhibits in situ adhesion of Helicobacter
pylori to human stomach. Phytomedicine 2007; 14: 285-288
[PMID: 17350240 DOI: 10.1016/j.phymed.2006.12.008]
118 Takagi A, Koga Y, Aiba Y, Kabir AM, Watanabe S, Ohta-
Tada U, Osaki T, Kamiya S, Miwa T. Plaunotol suppresses
interleukin-8 secretion induced by Helicobacter pylori:
therapeutic effect of plaunotol on H. pylori infection. J Gas-
troenterol Hepatol 2000; 15: 374-380 [PMID: 10824880 DOI:
10.1046/j.1440-1746.2000]
119 Asha MK, Debraj D, Prashanth D, Edwin JR, Srikanth HS,
Muruganantham N, Dethe SM, Anirban B, Jaya B, Deepak
M, Agarwal A. In vitro anti-Helicobacter pylori activity of a
flavonoid rich extract of Glycyrrhiza glabra and its probable
mechanisms of action. J Ethnopharmacol 2013; 145: 581-586
[PMID: 23220194 DOI: 10.1016/j.jep.2012.11.033]
120 Quílez A, Berenguer B, Gilardoni G, Souccar C, de Men-
donça S, Oliveira LF, Martín-Calero MJ, Vidari G. Anti-
secretory, anti-inflammatory and anti-Helicobacter pylori
activities of several fractions isolated from Piper carpunya
Ruiz & amp; Pav. J Ethnopharmacol 2010; 128: 583-589 [PMID:
20152892 DOI: 10.1016/j.jep.2010.01.060]
121 Chung JG, Tsou MF, Wang HH, Lo HH, Hsieh SE, Yen YS,
Wu LT, Chang SH, Ho CC, Hung CF. Rhein affects aryl-
amine N-acetyltransferase activity in Helicobacter pylori
from peptic ulcer patients. J Appl Toxicol 1998; 18: 117-123
[PMID: 9570694 DOI: 10.1002/(SICI)1099-1263(199803/04)]
122 Wang YC, Huang KM. In vitro anti-inflammatory effect of
apigenin in the Helicobacter pylori-infected gastric adeno-
carcinoma cells. Food Chem Toxicol 2013; 53: 376-383 [PMID:
August 14, 2014|Volume 20|Issue 30|
 Wang YC. Medicinal plants and H. pylori -induced diseases
23266501 DOI: 10.1016/j.fct.2012.12.018]
123 Zaidi SF, Yamamoto T, Refaat A, Ahmed K, Sakurai H,
Saiki I, Kondo T, Usmanghani K, Kadowaki M, Sugiyama
T. Modulation of activation-induced cytidine deaminase by
curcumin in Helicobacter pylori-infected gastric epithelial
cells. Helicobacter 2009; 14: 588-595 [PMID: 19889077 DOI:
10.1111/j.1523-5378.2009.00724.x.]
124 Lee IO, Lee KH, Pyo JH, Kim JH, Choi YJ, Lee YC. Anti-
inflammatory effect of capsaicin in Helicobacter pylori-
infected gastric epithelial cells. Helicobacter 2007; 12: 510-517
[PMID: 17760719 DOI: 10.1111/j.1523-5378.2007.00521.x]
125 Abdel-Latif MM, Windle HJ, Homasany BS, Sabra K,
Kelleher D. Caffeic acid phenethyl ester modulates Helico-
bacter pylori-induced nuclear factor-kappa B and activator
protein-1 expression in gastric epithelial cells. Br J Phar-
macol 2005; 146: 1139-1147 [PMID: 16247412 DOI: 10.1038/
sj.bjp.0706421]
126 Shih YT, Wu DC, Liu CM, Yang YC, Chen IJ, Lo YC. San-
Huang-Xie-Xin-Tang inhibits Helicobacter pylori-induced
inflammation in human gastric epithelial AGS cells. J Ethno-
pharmacol 2007; 112: 537-544 [PMID: 17537603 DOI: 10.1016/
j.jep.2017.04.015]
127 Zaidi SF, Muhammad JS, Shahryar S, Usmanghani K, Gilani
AH, Jafri W, Sugiyama T. Anti-inflammatory and cyto-
protective effects of selected Pakistani medicinal plants in
Helicobacter pylori-infected gastric epithelial cells. J Ethno-
pharmacol 2012; 141: 403-410 [PMID: 22433535 DOI: 10.1016/
j.jep.2012.03.001]
128 Toyoda T, Tsukamoto T, Takasu S, Shi L, Hirano N, Ban
H, Kumagai T, Tatematsu M. Anti-inflammatory effects
of caffeic acid phenethyl ester (CAPE), a nuclear factor-
kappaB inhibitor, on Helicobacter pylori-induced gastritis
in Mongolian gerbils. Int J Cancer 2009; 125: 1786-1795 [PMID:
19610061 DOI: 10.1002/ijc.24586]
129 Wu H, Li W, Wang T, Shu Y, Liu P. Paeoniflorin suppress
NF-kappaB activation through modulation of I kappaB
alpha and enhances 5-fluorouracil-induced apoptosis in hu-
man gastric carcinoma cells. Biomed Pharmacother 2008; 62:
659-666 [PMID: 18809274 DOI: 10.1016/j.biopha.2008.08.002]
130 Jang SH, Lim JW, Kim H. Beta-carotene inhibits Helico-
bacter pylori-induced expression of inducible nitric oxide
synthase and cyclooxygenase-2 in human gastric epithelial
AGS cells. J Physiol Pharmacol 2009; 60 Suppl 7: 131-137
[PMID: 20388956]
WJG|www.wjgnet.com
131 Foryst-Ludwig A, Neumann M, Schneider-Brachert W, Nau-
mann M. Curcumin blocks NF-kappaB and the motogenic re-
sponse in Helicobacter pylori-infected epithelial cells. Biochem
Biophys Res Commun 2004; 316: 1065-1072 [PMID: 15044093
DOI: 10.1016/j.bbrc.2004.02.158]
132 Kataoka M, Hirata K, Kunikata T, Ushio S, Iwaki K, Ohashi
K, Ikeda M, Kurimoto M. Antibacterial action of tryptan-
thrin and kaempferol, isolated from the indigo plant (Po-
lygonum tinctorium Lour.), against Helicobacter pylori-in-
fected Mongolian gerbils. J Gastroenterol 2001; 36: 5-9 [PMID:
11211212 DOI: 10.1007/s005350170147]
133 González-Segovia R, Quintanar JL, Salinas E, Ceballos-
Salazar R, Aviles-Jiménez F, Torres-López J. Effect of the
flavonoid quercetin on inflammation and lipid peroxidation
induced by Helicobacter pylori in gastric mucosa of guinea
pig. J Gastroenterol 2008; 43: 441-447 [PMID: 18600388 DOI:
10.1007/s00535-008-2184-7]
134 Liu BH, Lee YK. Effect of total secondary carotenoids ex-
tracts from Chlorococcum sp on Helicobacter pylori-infected
BALB/c mice. Int Immunopharmacol 2003; 3: 979-986 [PMID:
12810355 DOI: 10.1016/S1567-5769(03)00096-1]
135 Matsubara S, Shibata H, Ishikawa F, Yokokura T, Takahashi
M, Sugimura T, Wakabayashi K. Suppression of Helicobacter
pylori-induced gastritis by green tea extract in Mongolian
gerbils. Biochem Biophys Res Commun 2003; 310: 715-719 [PMID:
14550260 DOI: 10.1016/j.bbrc.2003.09.066]
136 Iimuro M, Shibata H, Kawamori T, Matsumoto T, Arakawa
T, Sugimura T, Wakabayashi K. Suppressive effects of garlic
extract on Helicobacter pylori-induced gastritis in Mongo-
lian gerbils. Cancer Lett 2002; 187: 61-68 [PMID: 12359352
DOI: 10.1016/S0304-3835(02)]
137 Pastene E, Speisky H, García A, Moreno J, Troncoso M,
Figueroa G. In vitro and in vivo effects of apple peel poly-
phenols against Helicobacter pylori. J Agric Food Chem 2010;
58: 7172-7179 [PMID: 20486708 DOI: 10.1012/jf100274g]
138 Mahady GB, Bhamarapravati S, Adeniyi BA, Doyle B, Lock-
lear T, Slover C, Pendland S. Traditional Thai medicines
inhibit Helicobacter pylori in vitro and in vivo: Support for
ethnomedical use. Ethnobot Res Appl 2006; 4: 159-165
139 Kuo CH, Weng BC, Wu CC, Yang SF, Wu DC, Wang YC.
Apigenin has anti-atrophic gastritis and anti-gastric cancer
progression effects in Helicobacter pylori-infected Mongo-
lian gerbils. J Ethnopharmacol 2014; 151: 1031-1039 [PMID:
24374236 DOI: 10.1016/j.jep.2013.11.040]
P- Reviewer: Balaban YH, Kanizaj TF, Zhu YL S- Editor: Ma YJ
L- Editor: A E- Editor: Ma S
10382 August 14, 2014|Volume 20|Issue 30|
 Published by Baishideng Publishing Group Inc
8226 Regency Drive, Pleasanton, CA 94588, USA
Telephone: +1-925-223-8242
Fax: +1-925-223-8243
E-mail: bpgoffice@wjgnet.com
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx
http://www.wjgnet.com

I S S N  1 0  0 7  -   9  3 2  7

3  0

9   7 7 1 0  0 7   9 3 2 0 45

© 2014 Baishideng Publishing Group Inc. All rights reserved.